Cancer Colorectal Clinical Trial
— CETIDYLOfficial title:
Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases. A Proof-of-concept Study
NCT number | NCT04189055 |
Other study ID # | FBH-001 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | January 7, 2020 |
Est. completion date | July 2024 |
The purpose of this study is to investigate the efficacy of cetuximab or cetuximab-irinotecan in patients with neo wild-type colorectal cancer who have been previously treated for metastatic disease. Patients will be included in cohort #1 or cohort #2. The inclusion in cohort #2 will start when the results of the cohort #1 are available. Patient will receive either cetuximab alone (cohort #1) or cetuximab with irinotecan (cohort #2).
Status | Recruiting |
Enrollment | 72 |
Est. completion date | July 2024 |
Est. primary completion date | April 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Provision of signed and dated informed consent and stated willingness to comply with all study procedures and availability for the duration of the study, 2. Male or female subjects, =18 years of age, 3. ECOG performance status (ECOG PS, Appendix 15.1) =2, 4. Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer, 5. At least one (=1) measurable and/or evaluable liver metastasis, 6. Prior therapy (resistant or intolerant) with fluoropyrimidines, oxaliplatin, irinotecan and antiangiogenic agent (ie, bevacizumab and/or aflibercept), 7. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: Hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL Adequate renal function: serum creatinine clearance (MDRD) = 50 mL/min/1,73 m2 Adequate liver function: serum bilirubin =1.5x upper normal limit (ULN), alkaline phosphatase <5xULN, AST and ALT =5xULN, Adequate serum electrolyte levels (magnesium, potassium, calcium) prior to initiation of study treatment, 8. Negative pregnancy test within 7 days prior to initiation of the study drug for female patients of childbearing potential, 9. Effective contraception for both male and female subjects if the risk of conception exists 10. Registration in a national health care system. Exclusion Criteria: 1. Known allergy or hypersensitivity reactions to any study drug, 2. Women who are pregnant or breastfeeding, 3. Inability to comply with study and follow-up procedures as judged by the Investigator, 4. Patient with BRAF mutant colorectal cancer 5. History of interstitial lung disease 6. Treatment with strong CYP3A4-enzyme inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John's wort for patients of cohort #2 7. Treatment with strong CYP3A4-enzyme inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) for patients of cohort #2 8. Treatment with strong UGT1A inhibitors (e.g. atazanavir, gemfibrozil, indinavir) for patients of cohort # 2 9. Patients of cohort #2 with known UGT1A deficiency 10. Uncontrolled illness, including but not limited to ongoing bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination/ clinical laboratory finding that leads to a reasonable suspicion of a disease/condition that contraindicates the use of any of investigational drugs that may affect the interpretation of the results, or that may render the subject at high risk of treatment complications. 11. Patient with current intestinal obstruction or history of chronic inflammatory bowel disease 12. Subjects under guardianship, curatorship or judicial protection |
Country | Name | City | State |
---|---|---|---|
France | Franco-British Hospital - GCS IHFB Cognacq-Jay | Levallois-Perret |
Lead Sponsor | Collaborator |
---|---|
GCS IHFB Cognacq-Jay |
France,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Tumor biomarkers | Tumor biomarkers will be tested : mismatch repair system (pMMR vs dMMR), HER1 (EGFR expression), HER2 expression, amphiregulin (AREG) and HER1 (EGFR GCN, cut-off 4.0), HER2, PI3KCA, PTEN, IRS2, | Assessed from study entry to end of study treatment, assessed up to 12 months after the beginning of the study | |
Primary | response rate | Tumor measurements will be obtained at baseline and every 8 weeks following treatment initiation. At the investigator's discretion, tumor assessments may be repeated at any time if progressive disease is suspected. Tumor response and progression will be assessed by the Investigator using RECIST v1.1. | 4 months | |
Secondary | Overall survival | OS is defined as the time interval from the date of inclusion to the date of death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period. | time interval from inclusion to the date of death from any cause. Assessed up to 12 months after the beginning of the study | |
Secondary | Progression-free survival | PFS is defined as the time interval from the date of inclusion to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at the last tumor assessment, either during study treatment period or during follow-up period. | the time interval from inclusion to the date of first documented disease progression or death from any cause, whichever occurs first. Assessed up to 12 months after the beginning of the study | |
Secondary | Disease Control rate | Disease control rate (DCR) is defined as the percentage of patients achieving CR, PR, or stable disease (SD). | from baseline until end of treatment, assessed up to 12 months after the beginning of the study | |
Secondary | Tolerance | Frequency of adverse events using NCI-CTCAE v5.0 | Assessed from study entry to 1 month after last study drug administration, assessed up to 12 months after the beginning of the study |
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